1. Technical Field of the Invention
The present invention relates to the application of chromophore compositions to the skin prior to laser treatment thereof. The thermal effects generated during the laser treatment are principally responsible for tissue ablation.
2. Description of the Prior Art
The nature of the interactions between the light emitted by a laser and biological tissue is complex and depends on numerous factors. At the present time, each pathology, disorder or unaesthetic characteristic of the skin requires a specific type of laser, the selection of which depends essentially on the objective which is to be achieved and the effect which is to be produced.
In particular, ablation of the outer layers of the skin (possibly extending as far as the dermis) with the aid of a laser, or smoothing of the skin, is carried out only with lasers emitting in the infrared spectrum and, thus, having a wavelength which is predominantly absorbed by water. However, the distribution of water in the skin depends on the site in question, the type of skin and the age of the individual who is to be treated. It is therefore apparent that a laser treatment of the texture of the skin which targets intracellular water is not reproducible from one individual to another. Exemplary lasers which emit in the infrared spectrum and target intracellular water include CO.sub.2 (10.6 .mu.m), Er:YAG (2.94 .mu.m) and Ho:YAG (2.12 .mu.m) lasers.
Lasers which emit in the visible spectrum or in the near infrared (wavelengths from 400 nm to 1000 nm), having a large penetration depth in skin, are primarily employed for treating lesions of the vascular of pigmentary type, but cannot be used for smoothing of the skin. Exemplary lasers which emit in the visible spectrum include pulsed dye lasers (585 nm) for treating vascular lesions and doubled Nd:YAG lasers (532 nm) for treating pigmentary lesions.
The clinical and histological response of skin to being irradiated with light varies considerably depending on the type of laser and the wavelength which is used. A number of effects may be generated in the target, and they directly depend on the nature of the chromophore (absorption coefficient at a given wavelength, structure and chemical composition, etc.), on the energy per unit surface area (or flux) and on the power per unit surface area (or irradiance). Studying the interaction of radiation with biological tissues makes it possible to distinguish between a number of mechanisms which occur. In the field of dermatology, the use of lasers is principally based on two types of mechanism, either the thermal effect, where the light energy is converted into heat energy, or the mechanical effect, where the light creates shockwaves.
The thermal effect results from the biological tissue absorbing the light energy associated with the laser beam and the local dissipation of this light energy in the form of heat energy. For a given wavelength, the degree to which the tissues are heated depends on the flux and the irradiance. Depending on the strength of the heating, coagulation, carbonization or ablation of the cells constituting the biological tissue may be observed. The thermal action of the laser can be divided into three principal effects, depending on the extent to which the tissue is heated and the time over which this takes place:
(1) Hyperthermia is a moderate increase in temperature, heating the tissue to temperatures of from 41.degree. to 44.degree. C. over several minutes. This action triggers cell damage with the membranes disappearing and the enzymes being denatured;
(2) Coagulation corresponds to necrosis without immediate tissue destruction. The temperature which the tissue reaches ranges from 50.degree. to 100.degree. C., over a period of time on the order of one second. This action promotes dehydration with the tissues shrinking as a result of the proteins and collagen being denatured. The necrosis is irreversible but without immediate loss of substance;
(3) Ablation corresponds to a loss of substance. The various constituents of the tissue are removed as vapor. The temperature which is attained ranges from 100.degree. to 1,000.degree. C., over a relatively short period of time (on the order of one-tenth of a second). Between 100.degree. and 300.degree. C., the tissue is removed through explosive vaporization due to the vacuoles rupturing.
The thermal transition between the irradiated zone and the healthy zone is gradual, and histological examination makes it possible to distinguish between three zones which, from the one closest to the irradiated zone to the one furthest away, correspond to: a carbonization zone or a tissue ablation zone (release of intercellular carbon at 150.degree. C.), a coagulation zone and a hyperthermia zone.
When the heat energy is dissipated in the tissue, it may be important to match the laser irradiation period to a period referred to as the thermal relaxation time, in order to limit the thermal damage created in the adjacent tissues. From a physical point of view, this period of time is defined as the time which the tissue requires to reduce its excess temperature by 50% with respect to the initial temperature. If the duration of the laser irradiation is less than this relaxation time, the heat will not be able to diffuse inside the tissue and will remain confined in the irradiated volume. Furthermore, if, within this time, the energy deposited in the target is sufficient to increase it to a temperature very much in excess of 100.degree. C., this will cause local vaporization of the medium. The expansion of the vapor bubble inside the tissue which has remained cool generates thermoelastic waves of weak amplitude. This process of selective photothermolysis is, for example, used for treating angiodysplasias of the skin: the erythrocytes absorb the pulse, explode, are vaporized and the rapid expansion of this vapor causes the vessel to rupture, with extravasation of the blood. Applied to the surface, this technique makes it possible to remove the target tissue locally.
Furthermore, analysis of the absorption spectrum of the various tissues indicates that the optical penetration depth of the radiation depends on the wavelength. Thus, the dissipation of energy as heat takes place in an interactive volume which depends essentially on the penetration depth of the beam (irradiated zone), the diffusion and thermal conductivity coefficients of the affected tissues, the local vascularization and ability of the target to maintain the heat stored or to lose it.
As indicated above, the thermal effect is generally obtained with an irradiance less than about 10.sup.8 W/cm.sup.2, which corresponds to an emission time greater than or equal to about 10.sup.-5 s.
The mechanical effect is based on the possibility of concentrating a large quantity of light energy onto a sufficiently small area and for a sufficiently short period of time to cause optical breakdown of the medium. This optical breakdown results in the formation of a plasma, namely, an extensively ionized gas due to an irradiance greater than or equal to about 10.sup.8 W/cm.sup.2 (which corresponds to an emission time less than or equal to 10.sup.-7 s, namely, a duration which is 100 times shorter than in the case of a thermal effect). The generation of shockwaves, the cavitation phenomenon and jet formation are associated with the formation of this plasma. At the boundary between the ionized medium (plasma) and the external medium, a pressure gradient is produced which results in the formation of a shockwave that will propagate into the adjacent tissues. Following this phenomenon (50-150 ns after the pulse), cavitation appears, i.e., the formation of bubbles which, for a few hundreds of microseconds, experience an oscillatory process of expansion and collapse (the bubble collapsing on itself). During these collapses, since the pressure increases considerably inside the bubble, a new shockwave is emitted.
Finally, each collapse may cause the formation of a jet if the bubble is generated close to a solid wall (for example close to a bone). This jet may then be responsible for surface damage to the solid wall (localized erosion of the solid).
Thus, U.S. Pat. No. 5,423,803 describes a process for removing a fraction of the corneal layer from the human skin using lasers which emit in the infrared spectrum (Nd:YAG, 1064 nm; CO.sub.2, 10.6 .mu.m) and have an emission time less than or equal to 50 ns. Before the laser irradiation, a composition comprising chromophores is applied to the skin which is to be treated. By employing either ultrasound or a laser, these chromophores are inserted into the intracellular spaces of the corneal layer. This treated area of the skin is then irradiated by a laser beam having sufficient energy to ionize the chromophores (after optical breakdown). As described above, the ionization of the chromophore leads to the formation of shockwaves (mechanical effect) which are responsible for ablating the first three cellular levels of the corneal layer. Since this effect is based on the emission of shockwaves, it presents the drawback of generating undesired irreversible lesions in the tissues adjacent to the area which is treated. Furthermore, the effectiveness of this treatment is spatially and qualitatively limited by the penetration of the chromophores into the corneal layer.